The specific function of poxvirus nucleases is not known. Two roles have been postulated for these activities, one in replication and/or processing of the viral genome, the other in the inhibition of host DNA synthesis. As a direct extension of previous work and current studies it is planned to: (1) reexamine the process of poxvirus DNA replication with emphasis on the role of virion DNases, (2) establish the molecular basis for the rapid suppression of host DNA synthesis by vaccinia, and (3) investigate a transitory stimulation of host DNA synthesis with Shope fibroma virus, an agent involved in benign tumors. It now seems obvious that an in depth understanding of DNA replication must provide significant clues about the process of malignancy. Information sought from this project could explain the role of nucleases in DNA replication and virus cytopathology.